The first method for quantifying cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. Solid-phase extraction followed protein precipitation with acetonitrile. HPLC separation was achieved in 16 min via gradient elution. Electrospray ionization was utilized for cannabinoid detection; both positive (Δ9-tetrahydrocannabinol [THC], cannabinol [CBN]) and negative (11-hydroxy-THC [11-OH-THC], 11-nor-9-carboxy-THC [THCCOOH], cannabidiol [CBD], THC-glucuronide and THCCOOH glucuronide) polarity were employed with multiple reaction monitoring. Calibration by linear regression analysis utilized deuterium-labeled internal standards and a 1/x2 weighting factor, yielding R2 values > 0.997 for all analytes. Linearity ranged from 0.5–50 μg/L (THC-glucuronide), 1.0–100 μg/L (THC, 11-OH-THC, THCCOOH, CBD and CBN) and 5.0–250 μg/L (THCCOOH-glucuronide). Imprecision was < 10.5% CV, recovery was > 50.5% and bias within ± 13.1% of target for all analytes at three concentrations across the linear range. No carryover, endogenous or exogenous interferences were observed. This new analytical method should be useful for quantifying cannabinoids in whole blood and further investigating cannabinoid glucuronides as markers of recent cannabis intake.
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